Chemfet array

ABSTRACT

An array of pixels, wherein each pixel comprises: a CHEMFET sensor; and a sigma delta ADC.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation of U.S. application Ser. No.16/346,999, filed May 2, 2019, which is a national stage filing under 35U.S.C. 371 of International Patent Application Serial No.PCT/GB2017/053304, filed Nov. 2, 2017. Foreign priority benefits areclaimed under 35 U.S.C. § 119(a)-(d) or 35 U.S.C. § 365(b) of Britishapplication number 1618749.4, filed Nov. 7, 2016. The entire contents ofthese applications are incorporated herein by reference in theirentirety.

This invention relates to improvements in or relating to the detectionof chemical and biological reactions in an electrolyte solution, usingsemiconductor-based devices; specifically, Ion-Sensing Field EffectTransistors (ISFETS).

It is well known to provide an array of pixels for detecting chemicaland biological reactions. The sensors used in such arrays aresemiconductor devices and a great deal of interest and research has goneinto the use of ISFET devices. ISFETs can be used to measure thehydrogen ion concentration or pH of an electrolyte solution. ISFETs arepopular because they can be fabricated within a conventionalComplementary Metal Oxide Semiconductor (CMOS) technology, resulting inlarge array of pH sensors alongside high resolution data acquisitioncircuits.

In order to measure and record these reactions, it is well known todivide the array into columns of pixels and to provide an Analogue toDigital Converter (ADC) for each column. This is known as columnparallel architecture and it has served the industry well for manyyears. The provision of a single ADC for each column reduces thehardware requirement as the ADC is configured to sample each of thepixels within a column, or multiple columns, sequentially therebybuilding up, over time, an output from each pixel.

It is against this background that the present invention has arisen.

According to the present invention there is provided an array of pixels,wherein each pixel comprises: a CHEMFET sensor; and an ADC. The CHEMFETsensor may be an ISFET sensor.

The provision of an ADC within each pixel allows the analogue to digitalconversion to take place within the pixel itself, rather than outsidethe pixel, as dictated by the column parallel architecture which formsthe status quo within the technical field.

The provision of an ADC within each pixel allows simultaneous samplingof the analogue signal generated by all of the ISFETs within the arrayand conversion of this into a digital signal that can be output fromeach pixel.

The provision of an ADC within each pixel means that space does not needto be allocated on the chip for ADCs outside the sensor array. Theprovision of the ADC within each pixel effectively frees up space on thechip in comparison with column parallel architecture.

A further advantage of the provision of the ADC within the pixel, isthat the array is fully scalable.

The ADC may be a sigma delta ADC, a SAR ADC, a Single-slope ADC, adual-slope ADC, a FLASH ADC or a pipelined ADC or a combination of theaforementioned architectures. The ADC may be differential or singleended. The sigma delta ADC may be advantageous because it provides ahigher resolution than other ADCs. A sigma delta ADC is alsoadvantageous because it is an over sampling ADC and this sampling isdone at a frequency much higher than the so-called “Nyquist” frequency,which is a frequency twice that of the signal bandwidth of interest. Thetechnical effect of such a high frequency is that noise prior to the ADCsampling is effectively folded down to lie with a frequency range of 0Hz to the half of the sampling frequency after sampling. This noise,together with the signal, then goes through a low pass decimation filterwith a cut-off frequency of the signal bandwidth of interest and thisfilter thereby removes almost all of the noise.

This is in contrast with other types of ADC where the noise only foldsdown at the lower sample frequency, which is equal to the Nyquistfrequency. As a result of this all of the noise is retained within thesignal.

The sigma delta ADC may be a single ended first order sigma delta ADCwhich has the advantage of providing the smallest available architecturetherefore enabling the invention to be implemented within the minimumpossible area. A 1-bit first order sigma delta ADC particularly lendsitself to incorporation within a pixel as all that is required tofacilitate the operation of such an ADC is an amplifier, a comparator, asample capacitor and an integration capacitor. The 1-bit first ordersigma delta ADC does not require any accurate analog components such astransistors, resistors or capacitors. The required components occupy asmaller silicon footprint than other ADCs. As a result, the pixel sizeis reduced in comparison with that which would be required toaccommodate other ADC types. Therefore the pixel density is increasedthereby providing more pixels within a fixed area.

Alternatively, the sigma delta ADC may be a second, third, fourth, fifthor sixth order sigma delta ADC.

Each pixel may further comprise bias control to control the amount ofcurrent in the pixel. The provision of the bias control within thepixel, rather than outside of the pixel is for noise control purposes asthe positioning of the bias control within the pixel prevents noise frompropagating from one pixel to the next through the bias control.

Each pixel may have an area in the region of 100 μm×100 μm, or 50 μm×50μm or 25 μm×25 μm, or 10 μm×10 μm or even 2.5 μm×2.5 μm. The pixel maybe square, or it may be rectangular. In order to increase the packingdensity of the pixels, hexagonal pixels may be used.

The array may comprise many pixels. There may be in the region of 4000pixels, or 6 million or even 100 million pixels. For example, the arraymay be 40×96 pixels or 256×160. Because the pixels each include an ADC,they are fully scalable and therefore can be formed into an array of anypractical size depending on the application for which the array will beused.

Each pixel may further comprise a switch configured to control the flowof data from the pixel onto a column on which each pixel is located.

Furthermore, according to the present invention there is provided a chipcomprising: an array of pixels as discussed above and a clockingarrangement comprising a first clock signal common to all of the pixelsin the array, for sampling the ISFET signal; and a second clock signalprovided sequentially across the array, for conversion of the signal.

The provision of a first clock signal that is common to all of thepixels enables the simultaneous sampling of the analogue ISFET signal ineach of the pixels.

The chip may be further configured to comprise control signals for eachpixel that enable the ISFET and the ADC within each pixel to be switchedon only when required. This provides considerable reduction in the powerrequired to operate the array and consequent efficiency improvements interms of unwanted heat within the array.

Furthermore, according to the present invention there is provided adevice comprising: an array of wells each configured to receive abiological or chemical substance, wherein the array of wells is providedover a chip as discussed above.

This configuration provides considerable advantages over the columnparallel architecture which forms the state of the art in this field, inthat it enables the sampling of the ISFET signals from all pixelssimultaneously. When the wells contain biological or chemical substancesin which reactions may be taking place, the sampling of all of the ISFETsignals at the same time ensures that the reactions taking place withinthe wells are all at the same point when the sample is taken. There istherefore no need to make allowances for differences in sample time whenall of the samples have been taken at the same time.

Once the sampling of all of the ISFETs has occurred simultaneously, thenthe conversion of the signal to a digital form may be staggered. If itis staggered then the entire pixel array is sampled at the same timewhilst minimising the peak current consumption of the array.

The invention will now be further and more particularly described, byway of example only, and with reference to the accompanying drawings, inwhich:

FIG. 1 shows a pixel block diagram;

FIG. 2 shows the connectivity of control signals and data output from anexemplary four pixels;

FIG. 3 is a pixel timing diagram;

FIG. 4 is an RVALID timing diagram;

FIG. 5 is a sigma delta ADC block diagram; and

FIG. 6 shows a device comprising a chip and an array of wells.

FIG. 1 is a pixel block diagram showing a single 100 μm square pixel 10which contains an ISFET 12, which is directly connected to a Sigma DeltaADC 14. The Sigma Delta ADC 14 is provided with ADC reference voltagesV_(REF) and is configured to perform the conversion of the analoguesignal from the ISFET 12 into a digital bitstream.

The pixel 10 also includes bias control 16 which receives a bias currentI_(B) from outside the pixel 10. The bias current I_(B) is in the regionof 0.1 μA to 100 μA, for example 2 μA and is used to provide biascontrol to the ISFET 12 and the Sigma Delta ADC 14.

The pixel 10 also includes a switch 18 which is configured to controlthe data output 0 from the pixel 10. When the switch 18 is activated, itconnects the data output 0 from the Sigma Delta ADC 14 to a column linewhich is provided outside the pixel 10.

FIG. 2 shows the connectivity of the control signals and data output foran exemplary set of four pixels 10. For reasons of clarity, the biascontrol has been omitted. The pixels 10 are each allocated a row andcolumn number. The data outputs of all of the pixels 10 in each columnn, n+1, n+2 etc. are connected. Each row of pixels is enumerated m, m+1,m+2 etc. A switched capacitor implementation of a single-ended firstorder sigma delta modulator is used as the ADC. The ISFET 12 is a sourcefollower NMOS floating gate transistor with its bulk tied to its source.In an alternative embodiment, not illustrated in the accompanyingdrawings, the single-ended first order sigma delta modulator is providedin a continuous time specification.

In the illustrated embodiment, the main control signals for the pixel 10are: CLK1, CLK2, CLK3, PIX_RSEL, SD_RSEL, and RVALID. CLK1 is used tosample the output from all of the ISFETs 12, while CLK2 and CLK3 areused to do the ADC conversion. PIX_RSEL and SD_RSEL are the row enablesignals for the ISFETs 12 and Sigma Delta ADCs 14, respectively. Thedata from the SD ADC 14 is arranged in columns and is controlled by thecorresponding RVALID signal, which indicates when data is valid on eachrow. To reduce power consumption, the pixels 10 are only turned on whenneeded.

One advantage of integrating the Sigma Delta ADC 14 into every pixel 10is that the entire pixel array 100 can be sampled at the same time,therefore capturing the output of all the ISFETs 12 at the same point intime for every frame capture. This is a very useful feature for when itcomes to processing the data, as allowances do not need to be made forthe difference in time capture of the samples when a column parallelarchitecture is used and the array is sampled row by row. To achievesimultaneous sampling of the entire array illustrated in FIG. 2, CLK1needs to be common to all the pixels. However, as CLK2 and CLK3 are onlyused to do the ADC conversion, they can be staggered between all thepixels 10 to reduce peak current consumption.

FIG. 3 is a timing diagram of the control signals. The ISFETs 12 are allsampled at the same time via CLK1<39:0>. Subsequently, the analogue todigital conversion takes place in a staggered fashion via CLK2<39:0> andCLK3<39:0>. The only difference between CLK2<m> and CLK3<m> is that thefalling edge of CLK3<m> occurs slightly before the falling edge ofCLK2<m> (for simplicity, only CLK3<0> has been shown in FIG. 3). Thepattern of CLK2 and CLK3 is repeated every 8th row as there isinsufficient time to stagger all 40 rows within an oversampling period.

To reduce power consumption, the ISFET 12 and ADC 14 blocks within thepixels 10 are only turned on when needed. This is achieved by turning onthe corresponding PIX_RSEL and SD_RSEL signals in advance of CLK1 andCLK2 respectively.

With reference to FIG. 4, as there is only one data pin for everycolumn, RVALID is used to latch the bitstream for each row of the pixelarray to the output pin. Data for each pixel is only valid when RVALIDis set high. RVALID_START is used to indicate the start of a new frame.All data collected within 2 RVALID_START pulses belong to the sameframe.

When the RVALID signals for all the rows are LOW, the column data lineis pulled to digital ground (GNDD) by a pull down resistor. Thisprevents the input to the digital controller from floating to anindeterminate voltage.

A block diagram of a single-ended first order sigma delta ADC is shownin FIG. 5. This ADC is based on a switched capacitor network andoperates at an oversampled frequency of 30 kHz. Assuming an oversamplingratio (OSR) of 512, the downsampled sample rate is thus just under 58.6Hz and the maximum signal bandwidth that recovered is no more than halfthat. In combination with a low-pass decimation filter with a cut-offfrequency of the signal bandwidth of interest, this results in the noisepresent before the sampling being folded down and then effectivelyeliminated by the low-pass decimation filter.

As will be apparent from FIG. 5, the negative reference voltage is setto the analogue ground (GNDA) to reduce the number of signals going intothe pixel 10. Both the positive reference voltage, VREFP, and the commonmode reference voltage, VCM, are buffered within each pixel 10 to reducenoise coupling across the rows of pixels 10 in the array 100.

It will further be appreciated by those skilled in the art that althoughthe invention has been described by way of example with reference toseveral embodiments it is not limited to the disclosed embodiments andthat alternative embodiments could be constructed without departing fromthe scope of the invention as defined in the appended claims.

1. An array of pixels, wherein each pixel comprises: a CHEMFET sensor;and a sigma delta ADC.
 2. The array of pixels according to claim 1,wherein the CHEMFET sensor is an ISFET sensor.
 3. The array of pixelsaccording to claim 1, wherein the sigma delta ADC is a single endedfirst order sigma delta ADC.
 4. The array of pixels according to claim1, wherein each pixel further comprises bias control.
 5. The array ofpixels according to claim 1, wherein each pixel has an area in theregion of 100 μm×100 μm.
 6. The array of pixels according to claim 1,wherein the array comprises in the region of 4000 pixels.
 7. The arrayof pixels according to claim 1, wherein each pixel further comprises aswitch configured to control the flow of data from the pixel.
 8. A chipcomprising: an array of pixels according to claim 2, and a clockingarrangement comprising: a first clock signal common to all of the pixelsin the array, for sampling the ISFET signal; and a second clock signalprovided sequentially across the array, for conversion of the signal. 9.The chip according to claim 8, further comprising control signals foreach pixel that enable the ISFET and the ADC within each pixel to beswitched on only when required.
 10. A device comprising an array ofwells each configured to receive a biological or chemical substance,wherein the array of wells is provided over a chip according to claim 8.11. The device according to claim 10, wherein each well covers more thanone pixel.
 12. The array of pixels according to claim 2, wherein thesigma delta ADC is a single ended first order sigma delta ADC.
 13. Thearray of pixels according to claim 12, wherein each pixel furthercomprises bias control.
 14. The array of pixels according to claim 13,wherein each pixel has an area in the region of 100 μm×100 m.
 15. Thearray of pixels according to claim 14, wherein the array comprises inthe region of 4000 pixels.
 16. The array of pixels according to claim15, wherein each pixel further comprises a switch configured to controlthe flow of data from the pixel.
 17. The array of pixels according toclaim 13, wherein each pixel further comprises a switch configured tocontrol the flow of data from the pixel.